Betaine is accumulated via transient choline dehydrogenase activation during mouse oocyte meiotic maturation

Abstract

Betaine (-trimethylglycine) plays key roles in mouse eggs and preimplantation embryos first in a novel mechanism of cell volume regulation and second as a major methyl donor in blastocysts, but its origin is unknown. Here, we determined that endogenous betaine was present at low levels in germinal vesicle (GV) stage mouse oocytes before ovulation and reached high levels in the mature, ovulated egg. However, no betaine transport into oocytes was detected during meiotic maturation. Because betaine can be synthesized in mammalian cells via choline dehydrogenase (CHDH; EC 1.1.99.1), we assessed whether this enzyme was expressed and active. transcripts and CHDH protein were expressed in oocytes. No CHDH enzyme activity was detected in GV oocyte lysate, but CHDH became highly active during oocyte meiotic maturation. It was again inactive after fertilization. We then determined whether oocytes synthesized betaine and whether CHDH was required. Isolated maturing oocytes autonomously synthesized betaine in the presence of choline, whereas this failed to occur in oocytes, directly demonstrating a requirement for CHDH for betaine accumulation in oocytes. Overall, betaine accumulation is a previously unsuspected physiological process during mouse oocyte meiotic maturation whose underlying mechanism is the transient activation of CHDH.

Embryo and cow factors affecting pregnancy per embryo transfer for multiple-service, lactating Holstein recipients

“…Perhaps stores of choline and its metabolites in the oocyte or de novo synthesis are adequate for the embryo to meet its needs. In mice, betaine is synthesized during oocyte development and is present in the preimplantation embryo ( McClatchie et al, 2017 ). It also has been observed that transcripts coding for enzymes involved in betaine and phosphatidylcholine synthesis are present during the preimplantation period in bovine embryos ( Jiang et al, 2014 ).…”

Quantitative Proteome Reveals Variation in the Condition Factor of Sea Urchin Strongylocentrotus nudus during the Fishing Season Using an iTRAQ-based Approach

“…CHDH is found in rat reproductive cells and has been shown to participate in mouse oocyte meiotic maturation. The deletion of CHDH decreased rat sperm motility [41,42]. Thus, the CHDH found in S. nudus gonads was deduced to take part in reproductive cell development during the fishing season.…”

Initiation of cell volume regulation and unique cell volume regulatory mechanisms in mammalian oocytes and embryos

“…As expected for betaine to function as an organic osmolyte, early embryos accumulate a greater amount of betaine with increased external osmolarity in vitro (Anas et al, 2007). One‐cell mouse embryos freshly isolated from the oviduct also contain considerable endogenous betaine, with measured amounts corresponding to ~10–20 mM (McClatchie et al, 2017). Thus, the endogenous amount of glycine (20–30 mM, above) plus that of betaine should be sufficient together to counterbalance about 30–50 mOsM of external osmolarity at their in vivo amounts.…”

“…Although SIT1 is inactive before fertilization, unfertilized eggs already contain essentially the same amount of endogenous betaine as 1‐ and 2‐cell embryos (Corbett et al, 2014; McClatchie et al, 2017). Endogenous betaine is present at low levels in GV‐intact oocytes but accumulates significantly during meiotic maturation (McClatchie et al, 2017), indicating that SIT1 cannot be responsible for the initial accumulation of betaine. The betaine in eggs is not due to prior transport since there is no measurable transport by oocytes.…”